Induction of Labour1

More than one in five births in England and Wales are consequent to labour induction and rates have increased steadily over the past two decades. The situation is similar in other parts of the world including the USA, Australia and other European countries. Given the high rates of caesarean section which are being seen in modern society, it becomes equally important to understand the efficacious methods of achieving vaginal delivery after a successful induction of labour.

Induction of labour is carried out for a number of clinical indications. The most common reasons include post-term pregnancy (defined as 41 + 0 weeks’ gestation), prelabour rupture of the amniotic membranes (PROM) or when the well-being of the woman or baby may be compromised by prolonging the pregnancy (e.g. in cases of foetal growth restriction or pre-eclampsia).

There are several choices when it comes to methods for induction of labour. These include pharmacological (e.g. oxytocin, misoprostol and prostaglandins), mechanical (e.g. Foley catheter) and complementary (e.g. acupuncture) methods. Each method has its unique advantages and disadvantages in terms of how quickly birth is achieved and the likelihood of complications.

Several factors influence the choice of agent—the reason for induction, its urgency, and the patient's obstetric and medical history. Choice may also be dictated by national guidelines, local protocols and patient choices. The National Institute for Health and Care Excellence (NICE) clinical guidelines (2008),¹ recommend vaginal prostaglandin E₂ (PGE₂) although neither the type of preparation (gel, tablet or sustained release pessary) nor the dose is specified.

Different induction methods incur different direct and indirect costs, with some methods requiring continuous monitoring throughout labour. Some methods are associated with increased risk of complications requiring a caesarean, and differ in rate of admission to neonatal intensive care units (NICU). There is evidence that inducing labour in women with complications is associated with lower health service costs compared with expectant management.2

The NICE Guidelines recommend that women should be informed that most women will go into labour spontaneously by 42 weeks. At the 38 week antenatal visit, all women should be offered information about the risks associated with pregnancies that last longer than 42 weeks, and their options.

Membrane sweeping involves the examining finger passing through the cervix to rotate against the wall of the uterus, to separate the chorionic membrane from the decidua. If the cervix will not admit a finger, massaging around the cervix in the vaginal fornices may achieve a similar effect. Sweeping is regarded as an adjunct to induction of labour rather than an actual method of induction.

The Bishop score is a group of measurements made by doing a vaginal examination, and is based on the station, dilation, effacement (or length), position and consistency of the cervix. A score of eight or more generally indicates that the cervix is ripe, or ‘favourable’—when there is a high chance of spontaneous labour, or response to interventions made to induce labour.

Prostaglandins are hormones produced naturally by the body that are important in the onset of labour. Synthetically manufactured prostaglandins have been used in clinical practice since the 1960s to ripen the cervix and induce uterine contractions. They are more frequently used in women when the cervix is unripe (i.e. with a Bishop score < 6).

Prostaglandins promote cervical ripening and encourage the onset of labour by acting on cervical collagen so as to encourage the cervix to soften and stretch in preparation for childbirth. Prostaglandins may also stimulate uterine contractions. Despite the widespread use of prostaglandins as part of labour induction, they can cause a number of side effects, including nausea, vomiting, diarrhoea and fever. In addition, because of their effect on the uterus, prostaglandins can cause contractions that last too long, or are too frequent or are too strong. Excessive uterine activity, or hyperstimulation, may be associated with foetal distress, and in a small number of cases can lead to uterine rupture, especially in those women who have uterine scarring from surgery or a previous caesarean birth.4

A large number of prostaglandin preparations have been available for labour induction, including prostaglandin F2 alpha (PGF2α, dinoprost), prostaglandin E2 (PGE2), prostaglandin E (PGE1) and misoprostol (a synthetic analogue of PGE1). In the past, PGF2α was frequently used in clinical practice but, more recently, PGE2 (dinoprostone) has become the most commonly used formulation. Commercially produced PGE2 analogues are expensive and require refrigeration.

Prostaglandins are available in a variety of formulations and doses, and may be given via various routes of administration, including vaginally, intracervically, orally and, less frequently, intravenously.

Vaginal PGE2 is the preferred method of induction of labour, unless there are specific clinical reasons for not using it (in particular the risk of uterine hyperstimulation). It should be administered as a gel, tablet or controlled release pessary.

Prostaglandin preparations for vaginal and intracervical administration include gels, lactose-based vaginal tablets, suppositories, pessaries or inserts. Dosages of prostaglandins (mainly PGE2) vary, depending on route and local protocol (frequently 0.5 mg for intracervical use, 2–3 mg for intravaginal use and 10 mg for sustained-release pessaries). There is also variation in terms of the number of applications and time intervals between repeated doses. Sustained-release vaginal pessaries have been developed to reduce the number of applications and vaginal examinations that are needed during induction of labour. Vaginal and intracervical administration are the most common forms of administration in current practice.

Tocolysis should be considered if hyperstimulation occurs during induction of labour.

Compared with placebo, several treatments reduced the odds of caesarean section, but they observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, vaginal misoprostol (≥ 50 µg) was most likely to 6increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost.

The active interventions most likely to achieve VD within 24 hours were intravenous (IV) oxytocin with amniotomy (mainly tested in trials recruiting women with favourable cervix), higher-dose ≥ 50 µg of vaginal misoprostol and vaginal prostaglandin E2 pessary (normal release).

Titrated (low-dose) oral misoprostol solution and sustained-release misoprostol vaginal pessary also performed well; however, there was greater uncertainty around the effect of these interventions for this outcome.

Compared with placebo, several treatments showed statistically significant reduction in the odds of caesarean section: titrated low-dose misoprostol, vaginal misoprostol at both ≥ 50 µg and < 50 µg, vaginal PGE2 gel, intracervical PGE2, oral misoprostol tablet (≥ 50 µg), Foley catheter, membrane sweeping and buccal/sublingual misoprostol.

Owing to the relatively high rates of hyperstimulation with buccal/sublingual misoprostol, PGE2 gel remains the method of choice as suggested by the NICE guidelines (2008). The fact that oral misoprostol is unlicensed for labour induction with virtually no pharmacokinetic data, poses a considerable research and ethical challenge. The risks of hyperstimulation with PGE2 gel are lower and the improvement in Bishop score is significant, as reflected in the rates of vaginal delivery within 24 hours. However, the NICE guidelines are up for review and we expect fresh guidance to be available next year which may show other methods of induction of labour in a more favourable light.